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Downloads/Storage-Summary.Pdf medRxiv preprint doi: https://doi.org/10.1101/2021.04.09.21255217; this version posted April 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 The Balancing Role of Distribution Speed against Varying Efficacy Levels of COVID-19 2 Vaccines under Variants 3 4 Daniel Kim 5 H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of 6 Technology, Atlanta, GA 30332, email: [email protected] 7 8 Pınar Keskinocak 9 H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of 10 Technology, Atlanta, GA 30332, email: [email protected] 11 12 Pelin Pekgün 13 Moore School of Business, University of South Carolina, Columbia, SC 29208, 14 email: [email protected] 15 16 Inci Yildirim 17 Department of Pediatrics, Section of Infectious Diseases and Global Health, Yale School of 18 Medicine and Yale Institute of Global Health, 1 Church Street, New Haven, CT 06510, 19 email: [email protected] 20 21 Corresponding Author: 22 Pınar Keskinocak 23 H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of 24 Technology, Atlanta, GA 30332, email: [email protected] 25 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.04.09.21255217; this version posted April 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 26 Abstract 27 28 Objective: Recent mutations in SARS-CoV-2 raised concerns about diminishing vaccine 29 effectiveness against COVID-19 caused by particular variants. Even with a high initial efficacy, 30 if a vaccine’s efficacy drops significantly against variants, or if it cannot be distributed quickly, it 31 is uncertain whether the vaccine can provide better health outcomes than other vaccines. Hence, 32 we evaluated the trade-offs between speed of distribution vs. efficacy of multiple vaccines when 33 variants emerge. 34 35 Methods: We utilized a Susceptible-Infected-Recovered-Deceased (SIR-D) model to simulate the 36 impact of immunization using different vaccines with varying efficacies and assessed the level of 37 infection attack rate (IAR) under different speeds of vaccine distribution. 38 39 Results: We found that a vaccine with low efficacy both before and after variants may 40 outperform a vaccine with high efficacy if the former can be distributed more quickly. 41 Particularly, a vaccine with 65% and 60% efficacy before and after the variants, respectively, can 42 outperform a vaccine with 95% and 90% efficacy, if its distribution is 46% to 48% faster (with 43 the selected study parameters). 44 45 Conclusions: Our results show that speed is a key factor to a successful immunization strategy to 46 control the COVID-19 pandemic even when the emerging variants may reduce the efficacy of a 47 vaccine. 48 medRxiv preprint doi: https://doi.org/10.1101/2021.04.09.21255217; this version posted April 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 49 Keywords: vaccination; disease modeling; COVID-19; vaccine efficacy; distribution speed 50 Preference for colors in Table 2, Figure 1, Figure 2, Figure 3: Online Only 51 Word Count 52 Word Count (Abstract): 200 Word Count (Text): 3404 53 Figure/Table Count: 5 References Count: 36 54 medRxiv preprint doi: https://doi.org/10.1101/2021.04.09.21255217; this version posted April 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 55 Introduction 56 Since the initial reports of a cluster of pneumonia cases of unidentified origin in Wuhan, 57 China, in December 2019, more than 133 million people around the world have been infected 58 with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the 59 development of effective vaccines in unprecedented speed, concerns have been raised on the 60 potential reduction in efficacy of these vaccines against the new SARS-CoV-2 variants due to 61 possible evasion from antibody recognition [1]. Most of the vaccines were developed and tested 62 before the new variants of SARS-CoV-2 emerged. In order to reach herd immunity, effective 63 implementation of a vaccine with sufficient efficacy against the circulating dominant variants is 64 essential. Subsequently, it becomes a trivial decision for policymakers and governments to favor 65 a vaccine with high efficacy for distribution. However, if the vaccine cannot be dispensed 66 quickly and/or if its efficacy drops significantly against the emerging variants compared to other 67 vaccines, the question of which vaccine should be favored is no longer trivial. Hence, the goal of 68 this study is to understand the tradeoffs between the speed of distribution vs. the change in the 69 efficacy levels of SARS-CoV-2 vaccines before and after the emergence of variants, which we 70 refer to as "initial efficacy" and "final efficacy", respectively, hereafter. 71 As of March 2021, twelve vaccines have received authorizations for emergency use around 72 the world [2]. Pfizer-BioNTech’s mRNA vaccine, which was the first authorized vaccine in the 73 United States, has an initial efficacy of 95% and needs to be stored at about minus 70 degrees 74 Celsius [3, 4]. Moderna’s mRNA vaccine has an initial efficacy of 94.5% and needs to be stored 75 at about minus 25 degrees Celsius [5]. Both mRNA vaccines require two doses with three to four 76 weeks apart application. Johnson & Johnson’s adenovirus-vectored vaccine has an average initial 77 efficacy of 66.3%, requires only a single dose, and needs to be stored at about 2-8 degrees medRxiv preprint doi: https://doi.org/10.1101/2021.04.09.21255217; this version posted April 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 78 Celsius [6]. Even though there are multiple authorized vaccines, their distribution and 79 administration have been slow. By the end of 2020, only 2.8 million people received the first 80 dose of COVID-19 mRNA vaccines in the United States [7]. Moreover, the Centers for Disease 81 Control and Prevention (CDC) reports that only about 10% of the population have been fully 82 vaccinated as of March 11, 2021 [8]. 83 In addition to distributional challenges, reduction in efficacy of vaccines against emerging 84 variants has raised concerns. As of March 2021, three main SARS-CoV-2 variants have been 85 identified. The B.1.1.7 variant, first identified in the United Kingdom in September 2020, caused 86 more than 28% of the infected cases in the United Kingdom in late December 2020, spread 56% 87 more quickly than other variants, and has become dominant in the United States [9, 10]. Another 88 variant B.1.351, first identified in South Africa in December 2020, has become dominant, 89 making up to 90% of infections, in South Africa and has been detected in several countries. The 90 last variant P.1 has been identified in Japan from travelers from Brazil in January 2021. In 91 response, scientists and vaccine manufactures have been testing the efficacy of the vaccines 92 against the variants and report that the B.1.1.7 variant is neutralized by most of the vaccines, 93 supporting the retention of the efficacy [11]. However, in vitro studies show that the vaccines’ 94 neutralization of B.1.351 variant is significantly lower than that of other variants [12, 13]. In 95 particular, the distribution of AstraZeneca’s adenovirus-vectored vaccine in South Africa has 96 been halted due to its low efficacy against the B.1.351 variant. Similarly, Novavax states that its 97 protein-based vaccine is 85.6% effective against the B.1.1.7 variant but 60% effective against the 98 B.1.351 variant [14]. 99 In this paper, we study the trade-offs between vaccines’ efficacy levels, which are subject to 100 reduction due to emerging variants and speed of vaccine distribution by using a modified medRxiv preprint doi: https://doi.org/10.1101/2021.04.09.21255217; this version posted April 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 101 Susceptible-Infected-Recovered-Deceased (SIR-D) model and simulating the infection attack 102 rate (IAR) under different times that the virus variants emerge. Throughout this paper, we refer 103 to vaccine distribution as the entire distribution process of a vaccine including delivery to the 104 dispensation sites and administration to the population.
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